Small molecules that modulate biological processes are powerful tools for analyzing complex biological systems, as well as potential lead compounds for human therapy. In the context of countermeasures against radiation, high-throughput small molecule screens could lead to a deeper understanding of the biological processes involved in radioprotection and to the discovery of new radioprotective reagents. A Small Molecule Screening and Medicinal Chemistry Core will be established to provide resources, instruments, and expertise for high-throughput screening of small molecule libraries for participants in the Dana Farber/Harvard Center for Medical Countermeasures against Radiation. The Core will help support a fully equipped screening facility, staffed by personnel with expertise in the development and implementation of high-throughput screens, as well as a medicinal chemistry group that will be able to take the first steps along a drug development pathway. To this end, the Core will leverage resources from the Harvard Medical School (HMS) ICCB-Longwood Screening Facility and will interact closely with other programs at HMS that share similar missions: the National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Disease (NSRB) and the Laboratory for Drug Discovery in Neurodegeneration (LDDN). The Small Molecule Screening Core, through ICCB-Longwood, will share access to small molecule libraries, expertise in organic chemistry, and use of computational resources with NSRB and LDDN. The Core will support multiple screening platforms and will establish a medicinal chemistry capability to advance the most promising hits identified by screening towards pharmaceutical development. The Specific Aims of the Small Molecule Screening and Medicinal Chemistry Core are: 1. to provide access for all Center participants to a small molecule HTS facility for screening pure protein and cell-based assay systems, 2. to facilitate the discovery of small molecule research tools to study radioprotection-relevant biological processes, 3. to provide medicinal chemistry expertise for maturation of interesting "hit" compounds into potential novel therapeutic leads with radioprotective activity.